TY - JOUR
T1 - Length polymorphism in heme oxygenase-1 is associated with arteriovenous fistula patency in hemodialysis patients
AU - Lin, C. C.
AU - Yang, W. C.
AU - Lin, S. J.
AU - Chen, T. W.
AU - Lee, W. S.
AU - Chang, C. F.
AU - Lee, P. C.
AU - Lee, S. D.
AU - Su, T. S.
AU - Fann, C. S.J.
AU - Chung, M. Y.
N1 - Funding Information:
We thank the following clinicians who referred the patients and collected blood samples: Dr Yee-Yung Ng, Dr Tsai-Hun Wu, Dr Der-Cherng Tarng, Dr Jinn-Yang Chen, Dr Yao-Ping Lin, and Dr Chiao-Lin Chuang at Taipei Veterans General Hospital; Dr Hong Hsiang Liou at Shin-Jen Hemodialysis Center; Hai-Ming Sheng at Wen-Lin Hemodialysis Center, Jeng Hu at Hwa-Jong Hemodialysis Center. We also thank Mei-Shiang Wang for technical support. This work was supported by a grant (2004-A042) from Taipei Veterans General Hospital and the Integrated Genome Project (2005-E02) of Taipei Veterans General Hospital in Taiwan.
PY - 2006/1
Y1 - 2006/1
N2 - Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation, producing carbon monoxide (CO), which carries potent antiproliferative and anti-inflammatory effects in the vascular walls. Transcription of the HO-1 gene is regulated by the length polymorphism of dinucleotide guanosine thymine repeat (GT)n in the promoter region, which was measured in this study to determine its association with arteriovenous fistula (AVF) failure in Chinese hemodialysis (HD) patients in Taiwan. L allele means (GT)n ≥ 30 and S allele means (GT)n < 30. Therefore, there are two L alleles for L/L genotype, one L and one S allele for L/S genotype, and two S alleles for S/S genotype. Among the 603 HD patients who were enrolled in this study, 178 patients had history of AVF failure, while 425 patients did not. Significant associations were found between AVF failure and the following factors (hazard ratio): longer HD duration (1.004 month), lower pump flow (0.993 ml/min), higher dynamic venous pressure (1.010 mmHg), location of AVF on the right side (1.587 vs left side) and upper arm (2.242 vs forearm), and L/L and L/S genotypes of HO-1 (2.040 vs S/S genotype). The proportion of AVF failure increased from 20.3% in S/S genotype and 31.0% in L/S genotype to 35.4% in L/L genotype (P = 0.011). Relative incidences were 1/87.6 (1 episode per 87.6 patient-months), 1/129, and 1/224.9 for HD patients with L/L, L/S, and S/S genotypes, respectively (P < 0.002). The unassisted patency of AVF at 5 years decreased significantly from 83.8% (124/148) to 75.1% (223/297) and 69% (109/158) in S/S, L/S, and L/L genotypes, respectively (P < 0.0001). In comparison with HD patients with S/S genotype, those with L/L genotype had a higher prevalence of coronary artery disease (29.1 vs 14.2%; P = 0.005). A longer length polymorphism with (GT) n ≥ 30 in the HO-1 gene was associated with a higher frequency of access failure and a poorer patency of AVF in HD patients. The longer GT repeat in the HO-1 promoter might inhibit gene transcription, and consequently offset the CO-mediated protective effect against vascular injury.
AB - Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation, producing carbon monoxide (CO), which carries potent antiproliferative and anti-inflammatory effects in the vascular walls. Transcription of the HO-1 gene is regulated by the length polymorphism of dinucleotide guanosine thymine repeat (GT)n in the promoter region, which was measured in this study to determine its association with arteriovenous fistula (AVF) failure in Chinese hemodialysis (HD) patients in Taiwan. L allele means (GT)n ≥ 30 and S allele means (GT)n < 30. Therefore, there are two L alleles for L/L genotype, one L and one S allele for L/S genotype, and two S alleles for S/S genotype. Among the 603 HD patients who were enrolled in this study, 178 patients had history of AVF failure, while 425 patients did not. Significant associations were found between AVF failure and the following factors (hazard ratio): longer HD duration (1.004 month), lower pump flow (0.993 ml/min), higher dynamic venous pressure (1.010 mmHg), location of AVF on the right side (1.587 vs left side) and upper arm (2.242 vs forearm), and L/L and L/S genotypes of HO-1 (2.040 vs S/S genotype). The proportion of AVF failure increased from 20.3% in S/S genotype and 31.0% in L/S genotype to 35.4% in L/L genotype (P = 0.011). Relative incidences were 1/87.6 (1 episode per 87.6 patient-months), 1/129, and 1/224.9 for HD patients with L/L, L/S, and S/S genotypes, respectively (P < 0.002). The unassisted patency of AVF at 5 years decreased significantly from 83.8% (124/148) to 75.1% (223/297) and 69% (109/158) in S/S, L/S, and L/L genotypes, respectively (P < 0.0001). In comparison with HD patients with S/S genotype, those with L/L genotype had a higher prevalence of coronary artery disease (29.1 vs 14.2%; P = 0.005). A longer length polymorphism with (GT) n ≥ 30 in the HO-1 gene was associated with a higher frequency of access failure and a poorer patency of AVF in HD patients. The longer GT repeat in the HO-1 promoter might inhibit gene transcription, and consequently offset the CO-mediated protective effect against vascular injury.
KW - Arteriovenous fistula
KW - Heme oxygenase-1
KW - Hemodialysis
KW - Polymorphism
KW - Stenosis
UR - http://www.scopus.com/inward/record.url?scp=30944442094&partnerID=8YFLogxK
U2 - 10.1038/sj.ki.5000019
DO - 10.1038/sj.ki.5000019
M3 - Article
C2 - 16374439
AN - SCOPUS:30944442094
SN - 0085-2538
VL - 69
SP - 165
EP - 172
JO - Kidney International
JF - Kidney International
IS - 1
ER -